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Cell Reports
Article . 2025 . Peer-reviewed
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Cell Reports
Article . 2025
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Cell Reports
Article . 2025
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Core fucosylation of IL-2RB is required for natural killer cell homeostasis

Authors: Harrison Sudholz; Xiangpeng Meng; Hae-Young Park; Zihan Shen; Iva Nikolic; Joseph Cursons; Ethan D. Goddard-Borger; +8 Authors

Core fucosylation of IL-2RB is required for natural killer cell homeostasis

Abstract

Natural killer (NK) cell homeostasis and effector functions require context-dependent signaling via numerous receptors, including the interleukin-15 receptor (IL-15R). Post-translational modifications can regulate receptor signaling, impacting receptor turnover and trafficking. Core fucosylation is one such modification known to impact receptor expression and is uniquely mediated by fucosyltransferase 8 (FUT8). We identified FUT8 as an essential gene required for IL-15R responsiveness in a human NK cell genome-wide CRISPR screen. To further validate core fucosylation in IL-15R signaling and NK cell biology, mice lacking Fut8 in NK cells (Fut8fl/flNcr1cre/+) were generated. The loss of core fucose in murine NK cells resulted in severe NK cell lymphopenia, with a reduction in IL-15Rβ (IL-2RB/CD122) expression, impairing in vivo homeostatic proliferation. The loss of FUT8 also decreased NK cell cytotoxicity, tumor immunity, and early viral immunity. Taking these results together, we have identified FUT8 as a key modulator of NK cell biology by regulating their development, IL-15R expression, and signaling.

Keywords

Mice, Knockout, QH301-705.5, CP: Immunology, Fucosyltransferases, Killer Cells, Natural, Interleukin-2 Receptor beta Subunit, Mice, Inbred C57BL, Mice, Animals, Homeostasis, Humans, Biology (General), Fucose, Signal Transduction

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    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Top 10%
Average
Top 10%
gold